Sitagliptin Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Sitagliptin Tablets contain an amount of sitagliptin phosphate (C₁₆H₁₅F₆N₅O · H₃PO₄) equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of sitagliptin (C₁₆H₁₅F₆N₅O).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Buffer: 1.36 g/L of monobasic potassium phosphate, adjusted with phosphoric acid to a pH of 2.0 Mobile phase: Acetonitrile and Buffer (15:85)

Solution A (IRA 1-Apr-2024) : Transfer 1 mL of phosphoric acid to a 1-L volumetric flask, and dilute with water to volume. Diluent: Acetonitrile and Solution A (IRA 1-Apr-2024) (5:95)

Standard solution: 0.1 mg/mL of USP Sitagliptin Phosphate RS in Diluent

Sample stock solution: Nominally 1.0 mg/mL of sitagliptin, prepared as follows. Place 10 Tablets in a suitable volumetric flask, and dilute with Diluent to volume. Add a stir bar and stir vigorously for 1 h, ensuring that a vortex is achieved during stirring.

Sample solution: Nominally 0.08 mg/mL of sitagliptin, prepared as follows. Transfer 8.0 mL of the Sample stock solution to a 100-mL volumetric flask, and dilute with Diluent to volume. Centrifuge a portion of the solution for 10 min or until the solution is clear, and use the supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 205 nm. For Identification A use a diode array detector in the range of 210–400 nm. Column: 4.6-mm × 15-cm; 5-µm packing L10

Column temperature: 30° Flow rate: 1 mL/min Injection volume: 20 µL

System suitability

Sample: Standard solution Suitability requirements

Relative standard deviation: NMT 1.0% (IRA 1-Apr-2024)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sitagliptin (C H F N O) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of sitagliptin (IRA 1-Apr-2024) from the Sample solution

r_S = peak response of sitagliptin (IRA 1-Apr-2024) from the Standard solution

C_S = concentration of USP Sitagliptin Phosphate RS in the Standard solution (mg/mL)

C_U = nominal concentration of sitagliptin in the Sample solution (mg/mL)

M_r1 = molecular weight of sitagliptin, 407.32

M_r2 = molecular weight of anhydrous sitagliptin phosphate, 505.31

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

DISINTEGRATION 〈701〉

Time: 5 min

Acceptance criteria: Meet the requirements

UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

5.1 ORGANIC IMPURITIES

Buffer, Mobile phase, Solution A (IRA 1-Apr-2024) , Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution (Procedure 1 may be used for Tablets containing sodium stearyl fumarate as an excipient in the formulation, and Procedure 2 may be used for all products.)

Procedure 1: Place 1 Tablet of any potency into a vial, add 1 mL of water, and tightly seal the vial. Heat at 80° for about 30 h to generate a

fumarate adduct of sitagliptin, N-succinyl sitagliptin. (IRA 1-Apr-2024) Transfer the contents of the vial into a 100-mL volumetric flask, using a small amount of Diluent, and dilute with Diluent to volume. Mix well by stirring for 1 h. If needed, further dilute with Diluent to obtain a solution with a concentration of 0.08 mg/mL of sitagliptin, based on the label claim of the Tablet. Centrifuge a portion of the solution for 10 min or until the solution is clear, and use the supernatant.

Procedure 2: Place 10 mg of USP Sitagliptin Phosphate RS and 1 mg of sodium stearyl fumarate into a vial, add 1 mL of water, and tightly seal the vial. Heat at 80° for about 30 h to generate a fumarate adduct of sitagliptin, N-succinyl sitagliptin. (IRA 1-Apr-2024) Transfer the contents of the vial into a 100-mL volumetric flask, using a small amount of Diluent, and dilute with Diluent to volume. Mix well by stirring for 1 h. Centrifuge a portion of the solution for 10 min or until the solution is clear, and use the supernatant.

Standard solution: 0.0002 mg/mL of USP Sitagliptin Phosphate RS in Diluent

Sensitivity solution: 0.0001 mg/mL of USP Sitagliptin Phosphate RS from Standard solution in Diluent System suitability

Samples: System suitability solution and Sensitivity solution

[NOTE—The relative retention times in Table 1 are provided as information that could aid in peak assignment.]

Table 1 (IRA 1-Apr-2024)

^a  (R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoic acid.

^b 2-{[(R)-4-Oxo-4-{3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-1-(2,4,5-trifluorophenyl)butan-2-yl]amino}succinic acid.

^c  This degradation product may be present only for Tablets containing sodium stearyl fumarate as an excipient in the formulation.

^d 10-(2,4,5-Trifluorobenzyl)-3-(trifluoromethyl)-6,7,10,11-tetrahydro-[1,2,4]triazolo[3,4-c][1,4,7]triazecine-8,12(5H,9H)-dione.

^e    (E)-1-{3-(Trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)but-2-en-1-one.

^f (E)-1-{3-(Trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)but-3-en-1-one. Suitability requirements

Resolution: NLT 1.5 between sitagliptin and N-succinyl sitagliptin, (IRA 1-Apr-2024) System suitability solution Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of any degradation product (IRA 1-Apr-2024) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × (M_r1/M_r2) × 100

r_U = peak response of each degradation product (IRA 1-Apr-2024) from the Sample solution

r_S = peak response of sitagliptin from the Standard solution

C_S = concentration of USP Sitagliptin Phosphate RS in the Standard solution (mg/mL)

C_U = nominal concentration of sitagliptin in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

M_r1 = molecular weight of sitagliptin, 407.32

M_r2 = molecular weight of anhydrous sitagliptin phosphate, 505.31

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at controlled room temperature.

USP REFERENCE STANDARDS 〈11〉

USP Sitagliptin Phosphate RS